CISMM

Microfluidics has emerged as an important technology in many areas of biomedicine including, for example, cell cultures, cell sorting, single cell analysis, amongst others. CISMM has employed microfluidics for molecular and cell experiments and provided training to collaborators and training to outside users within our yearly Workshop on Forces in Biology. Within the Thromboses Collaboration Cluster, we are developing microfluidic channels that incorporate magnetic pole tips to perform mechanical measurements of clots formed more closely to their native condition, under flow. Within the Lung Collaboration Cluster, we are developing microfluidic systems for cell cultures that replicate the converging geometry of the bronchioles to understand airway surface liquid volume regulation.

Clots under flow: In the Thromboses Collaboration Cluster, we have the goal of understanding clot formation and rupture from the molecular to the whole-clot scale. When clots begin inside blood vessels, they are formed under conditions different from static wells in microtiter plates or in capillary tubes. Flow imparts forces that can align fibers during formation, affecting network formation, and alter biochemical concentrations as flows redistribute around the forming thrombi. In understanding the failure of thrombi, it is critical to place the clots under the shear stresses similar to those inside vessels. We have begun to image the structure and distortion of fibrin networks formed under flow in microfluidic chambers We have extensive lithography capabilities within our group to produce new masks, masters and channels with rapid turn-around times.

Mucus Clearance Assay: The maintenance of a thickness of airway surface liquid over the epithelial surface is essential for the proper function of the mucus clearance system. The geometry of the lung, designed to optimize the surface area of the blood supply that is available for gas exchange, necessitates a severe challenge for controlling the fluid height during clearance. The lung geometry develops through a series of branching steps, or generations, through up to 23 bifurcations. This results in a huge number of branches at the termini, up to 223 ~ 107! This means a huge increase in surface area. For example, if the fluid volume was conserved in going from generation 14 to the trachea, there would be an increase in the height of the fluid by a factor of 600. A 20 micron thick layer of mucus at generation 14 would increase to 1.2 cm, choking off the airway. CISMM is developing a microfluidic channel that replicates the convergence of the lung and allows studies of coordinated clearance of mucus in cell cultures.